Contribution of antioxidants to preventive effect of mesna in cyclophosphamide-induced hemorrhagic cystitis in rats

Abstract

Purpose: The aim of this study was to evaluate whether combination of antioxidants and mesna may prevent cystitis induced by cyclophosphamide better than mesna alone.

Materials and methods: A total of 46 male Sprague-Dawley rats were divided into six groups. Five groups received single dose of cyclophosphamide (CP, 100 mg/kg) intraperitoneally with the same time intervals: group 2 received CP only, group 3 received mesna (21.5 mg/kg for three times), group 4 beta-carotene (20 mg/kg for two times) and mesna, group 5 received alpha-tocopherol (20 mg/kg for two times) and mesna, and group 6 received melatonin (5 mg/kg for two times) and mesna on the day of CP injection. Group 1 served as control.

Results: CP injection resulted in severe cystitis. Mesna has showed meaningful but not full protection against CP toxicity. Although beta-carotene did not show any additional beneficial effect when combined with mesna, alpha-tocopherol and especially melatonin with mesna resulted full protection that the pathologist, blinded to the slides, could not differ from sham control.

Conclusion: Oxidants may be important in the pathogenesis of CP-induced cystitis. Melatonin and alpha-tocopherol may help to ameliorate bladder damage along with other drugs such as mesna and diuretics.